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Depletion of Alveolar Macrophages by Treatment with 2-Chloroadenosine Aerosol

机译:通过2-氯路胞苷气雾剂治疗肺泡巨噬细胞耗竭。

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Alveolar macrophages (AMs) are localized in the alveoli and alveolar ducts of the lung and are the only macrophages living in an aerobic environment. Recent studies have demonstrated that AMs play a central role in lung diseases, such as pneumonia and acute respiratory distress syndrome. It has become important to find a simple, effective way to eliminate AMs in order to investigate the function of AMs in vivo. 2-Chloroadenosine (2-CA), a purine analog, is reported to be selectively cytotoxic to cultured macrophages, and we hypothesized that it would deplete the number of AMs in the bronchoalveolar lavage fluid (BALF) of mice without any effect on neutrophil or lymphocyte counts. After mice had inhaled 1 mM aerosolized 2-CA for 2 h, AMs were found to be significantly depleted at 0 h [(4.42 ± 0.16) × 104/ml], 24 h [(4.17 ± 0.89) × 104/ml], 48 h [(3.17 ± 0.21) × 104/ml], and 72 h [(5.00 ± 0.64) × 104/ml] compared with concentrations in untreated controls [(12.1 ± 0.21) × 104/ml]. Neutrophil and lymphocyte counts in BALF did not change and histological changes in the lung were not observed after 2-CA treatment. The lung wet-to-dry weight ratio did not change at 0, 24, and 48 h after 2-CA aerosol application. The 2-CA aerosol had no effect on lung vascular permeability, as assessed by the intravenous administration of Evans blue, or on other phagocytes, as assessed by Kupffer cell counts. Our study demonstrates the efficacy of 2-CA in reducing AM numbers in vivo.
机译:肺泡巨噬细胞(AMs)位于肺的肺泡和肺泡导管中,并且是生活在有氧环境中的唯一巨噬细胞。最近的研究表明,AMs在肺部疾病如肺炎和急性呼吸窘迫综合征中起着核心作用。为了研究AM在体内的功能,找到一种简单有效的消除AM的方法已经变得很重要。据报道,嘌呤类似物2-氯路胞苷(2-CA)对培养的巨噬细胞具有选择性的细胞毒性,我们假设它会耗尽小鼠支气管肺泡灌洗液(BALF)中的AM数量,而对嗜中性粒细胞或淋巴细胞计数。小鼠吸入1 mM气雾化的2-CA 2小时后,发现AM在0 h [(4.42±0.16)×10 4 / ml],24 h [(4.17± 0.89)×10 4 / ml],48 h [(3.17±0.21)×10 4 / ml]和72 h [(5.00±0.64)×10 < sup> 4 / ml]与未处理对照组的浓度[(12.1±0.21)×10 4 / ml]进行比较。 2-CA治疗后,BALF中的中性粒细胞和淋巴细胞计数未改变,并且未观察到肺组织学改变。施用2-CA气雾剂后0、24和48小时,肺干重比没有变化。如静脉注射伊文思蓝所评估的,2-CA气雾剂对肺血管通透性没有影响,对库普弗细胞计数所评估的其他吞噬细胞没有影响。我们的研究证明了2-CA在体内减少AM数量方面的功效。

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